PROJECT SUMMARY/ABSTRACT Childhood obesity is the most serious public health problem of the 21st century, given the prevalence, global reach, and widespread health, economic, and social consequences. While weight gain at the most basic level is due to a chronic energy surplus, there are a host of influences that act on the energy balance system that remain largely unknown. Thus, there is a critical need to identify previously unexamined factors that may influence the energy balance system in order to develop effective interventions for prevention and treatment. Our long-term goal is to quantify the dynamic relationships between various physiological and psychological components of the energy balance system. Our short-term goal is to examine linkages between physical activity, appetite control, and energy metabolism in adolescents. The status quo as it relates to appetite control is that body weight status and related peripheral signals are a key regulator of energy intake. In contrast to body weight playing a primary role in energy regulation, our working hypothesis is that high levels of regular moderate-to-vigorous physical activity (MVPA) result in a metabolic phenotype consisting of enhanced metabolic function and proper regulation of appetite, which prevents the development of obesity. We have reported that adults with low levels of MVPA have dysregulated appetite control, evidenced by higher levels of energy intake and elevated levels of dietary disinhibition. Additionally, primary mentor Thyfault has observed that rats with low fitness possess dysregulated control of appetite and reduced hepatic fat oxidation compared to rats with high fitness. Based on these findings in adults and rodents, in addition to supportive work by others, we hypothesize that low levels of MVPA create a metabolic phenotype, leading to dysregulated appetite control which predisposes individuals to weight gain. To test this hypothesis we will perform two studies focused on the links between physical activity and appetite. For Study 1, we will assess metabolic function and appetite control in male and female adolescents stratified by bodyweight (normal vs overweight/obese) and physical activity (sedentary vs. active) using a 2 x 2 cross-sectional study design (N=40). For Study 2, we will examine the influence of MVPA on the same outcomes by randomly assigning sedentary overweight/obese adolescents (N=44) to either a structured-exercise group or no treatment control for three months. The specific aims of the proposed studies are: 1) To examine the association between physical activity and appetite control in adolescents, with metabolic function serving as a mediator; and, 2) To test if increased physical activity through an exercise intervention influences metabolic function and appetite control. At the completion of the proposed studies, it is our expectation that we will have described the independent effects of physical activity and body weight on energy metabolism and appetite in adolescents. This study will have a significant positive impact on the understanding of energy balance in adolescents, and will inform public health interventions that specifically target mechanisms associated with weight gain in youth. 1